Pembrolizumab for the treatment of patients with Bacillus Calmette-Guérin unresponsive, high-risk non–muscle-invasive bladder cancer: over two years follow-up of KEYNOTE-057
Pembrolizumab ( Keytruda ) was approved for the treatment of high-risk ( HR ) non–muscle-invasive bladder cancer ( NMIBC ) based on results from the phase 2 KEYNOTE-057 trial.
Researchers have presented safety, efficacy, and posttreatment outcomes with 2 years or more follow-up from KEYNOTE-057 cohort A.
Patients with histologically confirmed high-risk Bacillus Calmette-Guérin ( BCG )-unresponsive carcinoma in situ ( CIS ) with or without papillary tumors who received adequate BCG therapy and were ineligible for or opted out of radical cystectomy ( RC ) received Pembrolizumab 200 mg Q3W for up to 2 years or until disease recurrence, progression, or unacceptable toxicity.
The primary endpoint was complete response rate ( CRR ). Key secondary endpoints were duration of response ( DOR ) and safety.
Overall, 102 patients were initially enrolled, and 96 were included in the efficacy analysis. Median time from enrollment to data cut off was 28.4 months ( range, 18.2-40.5 ).
Complete response rate was 40.6% ( 95% CI, 30.7-51.1 ), and median duration of response was 16.2 months ( range, 0+ to 30.4+ ).
Among 39 patients with complete response, 18 ( 46.2% ) had a DOR greater than or equal to 12 months.
No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment.
Median progression-free survival ( PFS ) and overall survival ( OS ) were not reached.
At 12 months, PFS was 82.7% and OS was 97.9%.
A total of 36 patients (37.5%) underwent radical cystectomy after discontinuation from study treatment, which included 9 of 22 patients ( 40.9% ) who had recurrence after initial complete response and 27 of 57 ( 47.4% ) nonresponders.
Of the 36 who underwent radical cystectomy, 33 ( 91.6% ) had no pathological upstaging to MIBC and 3 ( 8.3% ) had at least pT2 disease at time of radical cystectomy.
For subsequent treatments other than radical cystectomy, 27 of 96 ( 28.1% ) patients received additional intravesical therapy ( eg, BCG, Gemcitabine, or Mitomycin ), 21 of 96 ( 21.9% ) underwent local procedures ( eg, TURBT ), and 3 of 96 ( 3.1% ) received systemic therapy ( eg, Pembrolizumab ).
In 102 patients treated with Pembrolizumab, treatment-related adverse effects ( TRAEs ) occurred in 67 ( 65.7% ) patients; most frequently reported TRAEs were fatigue, pruritus, and diarrhea ( 10.8% each ).
Grade 3/4 TRAEs occurred in 13 patients ( 12.7% ), and 21 patients ( 20.6% ) experienced immune-mediated adverse effects. There were no grade 5 TRAEs.
In conclusion, after more than 2 years of follow-up, durable and clinically meaningful activity of Pembrolizumab was observed in patients who had high-risk BCG-unresponsive carcinoma in situ with or without papillary tumors and who were ineligible for or opted out of radical cystectomy.
Pembrolizumab did not seem to limit the opportunity for subsequent therapies, including radical cystectomy.
The safety profile was consistent with what is reported in the literature. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020
Resected stage III melanoma with BRAF mutations: 5-year follow-up of adjuvant Dabrafenib plus Trametinib - Findings from the COMBI-AD study
Data from the five-year analysis featuring extended follow-up from the phase III COMBI-AD study have confirmed that 12 months of...
Efficacy and safety of Pembrolizumab plus chemotherapy to Pembrolizumab monotherapy: a consecutive analysis of NSCLC patients with high PD-L1 expression
There has been an only indirect comparison between Pembrolizumab ( Keytruda ) and Pembrolizumab plus chemotherapy in patients with non-small...
Primary Ipilimumab / Nivolumab immunotherapy followed by adjuvant Nivolumab in locally advanced or oligometastatic melanoma: preliminary results
The aim of neo-adjuvant therapy in locally advanced or oligometastatic melanoma is to facilitate radical resection, improve outcomes and undertake...
ALEX study: updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer
The ALEX study has demonstrated significantly improved progression-free survival ( PFS ) with Alectinib ( Alecensa ) versus Crizotinib (...
In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for...
The mRNA-1273 vaccine for SARS-CoV-2 is tolerable and immunogenic in older adults. Data on prolonged immunogenicity and effectiveness in preventing severe...
Ayvakyt for the treatment of adults with unresectable or metastatic PDGFRA D842V mutant gastrointestinal stromal tumors, approved by European Commission
The European Commission ( EC ) has granted conditional marketing authorization to Ayvakyt ( Avapritinib ) as a monotherapy for...
FDA has approved Ayvakit, the first targeted therapy to treat a rare mutation in patients with gastrointestinal stromal tumors
The FDA ( U.S. Food and Drug Administration ) has approved Ayvakit ( Avapritinib ) for the treatment of adults...
European Commission has approved expanded use of Erleada for treatment of patients with metastatic hormone-sensitive prostate cancer
The European Commission ( EC ) has granted marketing authorisation for the expanded use of Erleada ( Apalutamide ) to...
Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies
The coronavirus disease 2019 ( COVID-19 ) virus, emerged in December 2019, has spread rapidly, with cases now confirmed in...